Over the last decade, quantitative computed tomography (QCT) and volumetric QCT (vQCT) images have become important sources of quantitative information on cortical and trabecular bone density, bone geometry and whole bone strength in the central skeleton. Compartmental bone micro-architecture and strength in the peripheral skeleton are being obtained using newly deployed high-resolution peripheral QCT (HR-pQCT) scanners. Although these approaches are in wide use, their inherent value as clinical research tools will depend on two major factors: (i) the ability to seamlessly employ them in the multi-center setting and (ii) the ability to distill fundamental information on pathophysiology and treatment efficacy through apples to apples comparisons of the cohort studies and pharmacologic trials done thus far, a process hindered by the use of multiple scanner types and image analysis platforms. To address these two basic issues, we propose an innovative research program to establish metrics for standardization of vQCT and HR-pQCT acquisitions for future multi-center studies, as well as to provide standardized skeletal density and structural metrics to provide a basis for direct comparison across multiple cohort studies and clinical trials. This work will be carried out at UCSF under the joint direction of Drs Lang and Burghardt and at the Mayo Clinic under the leadership of Dr. Khosla and Dr. Keyak at UCI. This research program is embodied in the following specific aims: Specific Aim 1: Development of metrics to standardize QCT and HRpQCT acquisitions and analysis in multicenter studies. Specific Aim 2: Development of open-source image analysis metrics for vQCT incorporated as a plug-in NIH supported programs such as MIPAV.